Background:
Hypertension related to pregnancy is a common obstetric complication
observed in 7-8% of the antenatal cases in India. Vitamin D is involved
in the development of the placenta and feto-maternal wellbeing, thereby
helping in prevention of obstetric complication like hypertension in
pregnancy. It modulates various biochemical reactions in the body to
prevent abnormal placentation preventing pregnancy related hypertension. Materials and methods: A
cross sectional observational study was conducted on 120 antenatal
women between April 2017 – March 2018 in Mahatma Gandhi
Medical College and Research Institute. Based on blood pressure,
primigravidas were classified as Mild (Group 1) and Severe (Group 2).
Investigations for hypertensive disorders of pregnancy and serum
Vitamin D were done. Serum Vitamin D levels were classified into
deficiency, insufficiency (20-30ng/ml) and sufficiency (30-100ng/ml).
Statistical analysis was done using SPSS-17. Results: In this
study, among the primigravidas with hypertensive disorders of pregnancy
67.5% were Vitamin D deficient, 24.2% had insufficiency and 8.3% had
sufficient serum Vitamin D levels. It was also observed that the serum
Vitamin D levels were significantly low with an increase in the
pre-pregnancy BMI (P value – 0.002) and increase in blood
pressure (P value – 0.004). There was significant negative
correlation seen between serum vitamin D and blood pressure as we moved
from the mild to the severe hypertension group. Conclusion: With
lower levels of serum vitamin D, more was the severity of hypertension
in pregnancy. Obesity was also associated with severe vitamin D
deficiency in the present study.

Vitamin D is a precursor for several biochemical reactions in the body
and mainly involved in calcium-phosphorus metabolism and mineralisation
of the bones. Vitamin D unlike other vitamins does not require daily
supplementation; sunlight exposure replenishes the body stores. It is
commonly observed when people are subjected to inadequate sunlight
exposure, poor dietary habits, bedridden individuals and extremes of
age. Vitamin D is also involved in the development of the placenta and
feto-maternal wellbeing, thereby helping in prevention of obstetric
complication like hypertension in pregnancy[1].

Hypertension in pregnancy is a common obstetric complication leading to
signs like thrombocytopenia, elevated liver enzyme, haemolysis,
seizures and bleeding manifestations which account for the high
maternal morbidity and mortality. There have been several studies done
to find an association between hypertension related to pregnancy and
levels of calciferol in the body. Observations made by Bodnar LM et al
and Burris et al have suggested that low calciferol levels have
associated with an increased chance of developing gestational diabetes,
preterm births and preeclampsia[2,3]. Merewood A et al found
association of Vitamin D deficiency with increased rates of caesarean
section[4]. Bener A et al studied that hypovitaminosis D was associated
with 5 times higher chance of developing hypertension during
pregnancy[5]. The risk of the mothers giving birth to neonates which
were small for gestation age was also much higher when they had
suboptimal Vitamin D levels[6]. Vitamin D has a regulatory action on
centrally acting vasodilating agents and has been found to regulate
blood pressure. Vitamin D has also been found to modulate various
immunological agents and suppress autoimmune antibodies so as to
prevent abnormal placentation thereby preventing hypertension related
to pregnancy[7]. But on the contrary Anupama Dave et al (2016) felt
that there was no causal relationship between low vitamin D level and
adverse maternal and neonatal outcome in terms of hypertension,
anaemia, caesarean section rates, diabetes or bony pain[8].

Hence an effort was made to establish the relationship between serum
level of vitamin D in hypertensive disorders in pregnancy and if a
correlation exists between the serum level of vitamin D and the
severity of hypertensive disorder in pregnancy.

Aims

To find the correlation of serum Vitamin D levels with hypertensive
disorder in pregnancy.

Objectives

1. To estimate the serum Vitamin D levels in primigravida with
gestational age 28-40 weeks with hypertensive disorders of pregnancy.
2. To find a correlation between serum Vitamin D
levels and severity of hypertensive disorders of pregnancy.

Sample collection:
Primigravidas were classified as Mild (Group 1) and Severe (Group 2)
based on blood pressure[Group 1 - 140/90mm-159/109mm of Hg and Group 2
– greater than and equal to 160/110mm of Hg] as per ACOG
guidelines 2014. Patients with Group 1 form of hypertension were
observed for 6 hours after admission and if the blood pressure
continues to be >=140/90mm of Hg, they were diagnosed to have
hypertensive disorder of pregnancy and were considered for the study.
Among these primigravidas, based on the inclusion and exclusion
criteria, informed consent was obtained and single blood sample of 5ml
was collected for estimation of serum Urea, serum Creatinine, serum
Uric acid, serum Bilirubin, serum Proteins, SGOT, SGPT, ALP, LDH and
serum Vitamin D was done by chemiluminescence assay. Result obtained
were analysed. Serum Vitamin D levels were classified into deficiency
where value of vitamin D less than 20ng/ml, insufficiency (20-30ng/ml)
and sufficiency (30-100ng/ml).

This observational comparative study was conducted in the Department of
obstetrics and gynaecology, Mahatma Gandhi Medical College and Research
Institute, Puducherry. The demographic characteristics are described in
Table.1. The total number of participants in the study were n=120.
Among the participants, 67.5% had vitamin D deficiency, 24.2% had
Vitamin D insufficiency and 8.3% had Vitamin D sufficiency. It was
observed that 75% of the studied population had mild hypertension and
25% had severe hypertension based on ACOG 2014 guidelines. In the
population studied, 67.5% had Vitamin D deficiency irrespective to the
age, exposure to sunlight and first trimester BMI. Age and exposure to
sunlight did not bear any significance to the levels of serum Vitamin
D. On comparing the mean serum Vitamin D levels in the three BMI
groups, the obese group had significantly lower mean serum vitamin D
levels when compared to the overweight and normal groups. On comparing
the mean serum Vitamin D levels in the two blood pressure groups, the
blood pressure group 2 has significantly lower mean serum vitamin D
levels when compared to group 1. (Table.2) Overall, there was a
significant negative correlation between serum Vitamin D levels with
systolic blood pressure(p value- 0.015), diastolic blood pressure (P
value- 0.005) and mean arterial pressure (p value – 0.006)
respectively which was statistically significant (p value = 0.015).
This implies that with an increase in systolic, diastolic and mean
arterial blood pressure levels among primigravida in the third
trimester with hypertensive disorders of pregnancy, there is
significant reduction in serum Vitamin D levels. (Table.3) In Group 1,
there was a significant negative correlation between serum Vitamin D
levels with systolic blood pressure (P value- 0.032) but not with
diastolic blood pressure and mean arterial pressure respectively. In
Group 2, there was a significant negative correlation between serum
Vitamin D levels with systolic (P value – 0.007) and
diastolic blood pressure (p value- 0.002) respectively but not with
mean arterial pressure. Fig.1 scatter plot shows a 5% variability in
the Vitamin D levels, explained by the linear relationship between
systolic blood pressure and Vitamin D. It is seen that 6% of the
variability in the Vitamin D levels is explained by the linear
relationship between diastolic blood pressure and Vitamin D. (Fig.2) It
is seen that 6% of the variability in the Vitamin D levels is explained
by the linear relationship between mean arterial blood pressure and
Vitamin D(Fig.3)

Table-1: Distribution of
all variables: (n=120)

Maternal factors

Characteristics

Age in years - Mean (± SD)

24.9 (±3.5) years

Exposure to sunlight

Outdoor workers

Indoor workers

14(11.7%)

106(88.3%)

BMI- Mean(±SD) in kg/m2

29.82(±5.75)

BMI- n, (%)

Normal

25(20.8%)

Overweight

51(42.5%)

Obese

44(36.7%)

POG in weeks - Median(range)

38 (28-40) weeks

Blood Pressure Factors

Characteristics

Systolic in mm of Hg- Mean(+/- SD)

149.1 (± 10.6) mm of Hg

Diastolic in mm of Hg – Mean(+/- SD)

95.3 (± 6.7) mm of Hg

Mean arterial pressure(MAP) in mm of Hg – Mean(+/-
SD)

113.2 (± 7.5) mm of Hg

Blood Pressure group- n, (%)

Group 1*

90(75%)

Group 2**

30(25%)

Table-2: Distribution of
Serum Vitamin D groups among the other variable groups

The present study was undertaken to establish an association between
Vitamin D levels and hypertension in pregnancy in primigravidas between
28 – 40 weeks admitted to Mahatma Gandhi Medical College and
Research Institute between April 2017 and Mar 2018. 120 cases who were
admitted from the obstetrics and gynaecology OPD with high blood
pressures were taken and Vitamin D levels were assessed.

In the present study, it was observed that majority of the subjects had
suboptimal levels of serum Vitamin D. Almost 92% of the patients
recruited had Vitamin D levels less than 30 ng/ml. In northern India,
Jain V et al (2011)[9], Goel P et al (2016)[10], Agarwal S et al
(2016)[11] and Kumari et al (2017)[12] observed that the serum levels
of Vitamin D of most of their subjects had low values of vitamin D
during the last few weeks of gestation. (Table4) The mean age observed
among the cases was 24.9±3.5 years and Vitamin D deficiency
was more when the age was greater than and equal to 30 years (84.6%)
when compared the population less than 30 years (65.4%). Goel P et al
(2016) observed that the mean age among women with hypertensive
disorders of pregnancy was 25.48 years and that 83.3% of those subjects
were Vitamin D deficient[10] Dave A et al (2017) observed that pregnant
women below 30 years of age had higher odds of developing deficiency of
Vitamin D compared to the older population[8].The sunlight exposure was
also considered based on the whether the woman’s occupation
involved outdoor (more exposure) or indoor (less exposure) work. The
number of cases with vitamin D deficiency was compared. In the present
study, 88.33% had less exposure to sunlight which suggests that a
majority of our patients were involved with indoor work whereas only
11.67% had more exposure. Bener et al observed that 36.6% had more
exposure and 63.4% had less exposure [13]. In India, Dave A et al
(2016) and Kumari et al (2017) et al observed that 38.1% and 35% had
good exposure to sunlight and 61.9% and 65% had less exposure
respectively[8,12].

Table-4: Table showing
the distribution of serum Vitamin D levels in the patients in our study
when compared to others

Jain Vet al (2011)

Goel Pet al (2016)

Agarwal S et al (2016)

Kumariet al (2017)

Our study

Vitamin D deficiency

81.1%

92%

83.4%

77.09%

67.5%

Vitamin D insufficiency

11.6%

6%

11.1%

22.91%

24.2%

Vitamin D sufficiency

7.3%

2%

5.53%

8.3%

In the present study, on the basis of BMI, 36.67% were obese. It was
seen that among the obese subjects, 72.7% and 20.45% were Vitamin D
deficient and insufficient respectively which was significant (p value
- 0.002). Hence an inverse relationship between Vitamin D and
BMI was observed which could have been due to the fact that higher
levels of body fat hampered vitamin D absorption. It was also seen that
the finding from our study was in congruence with several other studies
as described. Bodnar et al (2007) also described that among the cases
studied, there was an increased rate of subnormal levels of Vitamin D
among the obese subjects (p value < 0.05) [14]. Zad ND et al
(2014) observed that 38% of their subjects fell under the obese
category and that there was a moderate negative correlation (p <
0.001) between BMI and serum levels of Vitamin D during the first
trimester [15]. Agarwal S et al (2016) observed in their study that
among the obese cases, 100% were Vitamin D deficient[11]. Pena HR et al
(2015) observed that among the obese subjects with normal blood
pressure, 32.5% were Vitamin D deficient and 47.5% had insufficient
Vitamin D levels. But when along with obesity, preeclampsia was also
considered, then 47.7% were Vitamin D deficient, 47.7% had Vitamin D
insufficient (P value -0.002)[16]. This showed that obesity by itself
was an independent risk factor for Vitamin D deficiency but when obese
individuals had associated preeclampsia, the risk only worsened.

In the present study, we found that the mean systolic blood pressure
was 149.1 (± 10.6) mm of Hg and the mean diastolic blood
pressure was 95.3 (± 6.7) mm of Hg. Among the group 1
subjects (mild hypertension), we found that 91% had suboptimal Vitamin
D levels, whereas in group 2 (severe hypertension) 100% of the subjects
had suboptimal serum Vitamin D levels (P value <0.001). The
initial research studied the likelihood of development of preeclampsia
on the basis of exposure to sunlight as it varies every season. It was
proposed that the amount of exposure to sunlight was directly
proportional to the Vitamin D produced in the body. Magnus et al (2001)
suggested that the chances of developing preeclampsia was more during
the winter months like December compared to the summer due to lesser
exposure to sunlight during the winter[17]. Whereas Algert et al (2010)
had a different concept as he felt that the amount of sunlight exposure
mattered more around the time of delivery which decreased the odds of
developing preeclampsia and not around conception. Algert et al also
felt that the prevalence of preeclampsia was less in less among those
who conceived in autumn compared to spring[18].The studies conducted
later emphasised more on the circulating serum levels of Vitamin D in
the body along with sunlight exposure to include the groups who were at
risk of developing Vitamin D deficiency. Bodnar et al (2007 and 2014),
Aghajafari et al (2009), Robinson et al (2010), Bener et al (2013) and
Hyppönen et al (2014) studied the relationship between serum
Vitamin D levels and various maternal outcomes comparing similar
parameters in different parts of the world. They all arrived at similar
conclusions wherein they observed that suboptimal Vitamin D in mothers
can lead to gestational diabetes mellitus, various forms of
hypertensive disorders of pregnancy and pregnancy induced
anaemia[19,2,20,21,5,6]. Aghajafari et al (2009) and Gernand et al
(2014) studied the neonatal outcomes along with the maternal
complications and concluded that maternal Vitamin D deficiency had a
higher risk of preterm infants and babies which were small for the
gestational age (SGA)[20,6]. Robinson et al (2010) and Bodnar et al
(2014) noted that their cases with severe preeclampsia were associated
with extremely low levels of vitamin D. The former observed that 54%
and 22% was Vitamin D deficient and insufficient respectively (p value
- 0.005); they also observed that a 10 ng/mL increase in Vitamin D was
associated with a 63% less chance of developing preeclampsia [21].
Whereas the latter observed that when patients attained Vitamin D of
more than 50nmol/L, there was a 40% less chance in developing severe
preeclampsia [2]. Bakacek Murat et al (2015) studied the Vitamin D with
respect to the severity of hypertensive disorders of pregnancy but
obtained no significant difference between the mild and the severe
forms although there were statistically significant findings when
compared to the controls [23]. When compared to our study, similar
findings were reported by Kumari et al (2017) in northern India such
that in cases with mild and severe preeclampsia, 95% and 100% had
suboptimal Vitamin D levels respectively with a combined p value
of <0.05. They also found a negative
correlation between Vitamin D at term and blood pressure with a
significant P value[12]. But contrary to all the above mentioned
studies, Dave A et al in a study conducted in northern India concluded
that their study showed no causal relationship between suboptimal
Vitamin D levels and maternal or neonatal complications [8].

Conclusion

Based on our results, it can be concluded that there is a significant
negative correlation between the serum vitamin D levels and
hypertensive disorders in pregnancy. The lower the serum vitamin D
levels, more is the severity of hypertension in pregnancy. It was also
observed that obesity is associated with severe vitamin D deficiency
which is evident from the drop in serum vitamin D levels as we move
from the normal to the obese BMI group. Hence there is a need for
supplementation of calciferol during pregnancy in order to reduce the
risk of serious maternal or neonatal outcome. Proper guidelines which
can recommend the apt dosage of supplementation when vitamin D
deficiency is diagnosed at different periods of gestation is required.

Author contributions:
Dr. Ashwin Rao is the principal investigator who conducted the study
Dr. Seetesh Ghose guided the principal investigator during the process
of the study.
Dr. Setu Rathod helped the principal investigator in the process of the
study and manuscript preparation.
We are grateful to all the patients for their cooperation during the
study process.

Scope for knowledge:
Vitamin D deficiency is a predisposing factor for hypertensive
disorders of pregnancy, gestational diabetes mellitus, preterm births
and various adverse obstetric outcomes. We were able to correlate the
grade of Vitamin D deficiency with the severity of hypertensive
disorders of pregnancy. This study also opens the scope for other
studies to come up with guidelines for proper supplementation of
Vitamin D right from the preconceptional period to prevent adverse
obstetric outcomes.